Supplementary Appendix

Transcription

1 Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Russo RJ, Costa HS, Silva PD, et al. Assessing the risks associated with MRI in patients with a pacemaker or defibrillator. N Engl J Med 2017;376: DOI: /NEJMoa

2 T A B L E O F C O N T E N T S P a g e 1 P a g e 2 P a g e 3 P a g e 4 P a g e 5 P a g e 7 P a g e 9 P a g e 10 P a g e 1 1 P a g e 1 3 C o o r d i n a t i n g C e n t e r, I n s t i t u t i o n s a n d I n v e s t i g a t o r s D a t a S a f e t y a n d M o n i t o r i n g B o a r d F u n d i n g S o u r c e s A c k n o w l e d g e m e n t s M a g n a S a f e P r o t o c o l D e s c r i p t i o n o f S t u d y E n d P o i n t s S t u d y P a r t i c i p a n t s C a s e o f G e n e r a t o r R e p l a c e m e n t S u p p l e m e n t a r y A p p e n d i x F i g u r e S 1 : M e a s u r e d C h a n g e s i n D e v i c e S e t t i n g V a l u e s ( P o s t - M R I m i n u s P r e - M R I ) S u p p l e m e n t a r y A p p e n d i x T a b l e S 1 : P a c e m a k e r m a n u f a c t u r e r s, m o d e l s, a n d c o u n t s f o r c a s e s P a g e 1 4 S u p p l e m e n t a r y A p p e n d i x T a b l e S 2 : I C D m a n u f a c t u r e r s, m o d e l s, a n d c o u n t s f o r c a s e s P a g e 1 5 P a g e 1 6 P a g e 1 7 P a g e 1 8 P a g e 1 9 P a g e 20 P a g e 2 1 S u p p l e m e n t a r y A p p e n d i x T a b l e S 3 : L i s t o f M a g n e t i c R e s o n a n c e S c a n n e r s b y M a n u f a c t u r e r a n d M o d e l S u p p l e m e n t a r y A p p e n d i x T a b l e S 4 : A r r h y t h m i a O n s e t O b s e r v e d D u r i n g o r I m m e d i a t e l y A f t e r M R I S u p p l e m e n t a r y A p p e n d i x T a b l e S 5 : E l e c t r i c a l R e s e t N o t e d A f t e r t h e M R I E x a m i n a t i o n S u p p l e m e n t a r y A p p e n d i x T a b l e S 6 : C o r r e l a t i o n s b e t w e e n P a c i n g L e a d I m p e d a n c e a n d a C h a n g e i n P - W a v e o r R - W a v e V o l t a g e o r P a c i n g L e a d T h r e s h o l d S u p p l e m e n t a r y A p p e n d i x T a b l e S 7 : C o r r e l a t i o n s b e t w e e n L e a d A g e a n d D e v i c e S e t t i n g C h a n g e s S u p p l e m e n t a r y A p p e n d i x T a b l e S 8 : R e p e a t M R I E x a m i n a t i o n s w i t h i n t h e M a g n a S a f e R e g i s t r y S u p p l e m e n t a r y A p p e n d i x T a b l e S 9 : Sec o n d a r y E n d P o i n t E v e n t s f o r P a c e m a k e r a n d I C D c a s e s W i t h a n d W i t h o u t a P r e v i o u s M R I V rjr

3 C O O R D I N A T I N G C E N T E R Robert J. Russo, MD, PhD, Principal Investigator Heather S. Costa, PhD, Research Scientist and Study Coordinator Patricia D. Silva, MS, Study Biostatis tician I N S T I T U T I O N S A N D I N V E S T I G A T O R S Abington Memorial Hospital, Abington, PA (Jennifer V. Frabizzio, MD) Advanced Cardiovascular Imaging, Carnegie Hill Radiology, NY, NY (Seth Uretsky, MD, Steven D. Wolff, MD, PhD) Allegheny General Hospital, Pittsburgh, PA (Robert W. W. Biederman, MD) Aurora St. Luke's Medical Center, Milwaukee, WI (Daniel C. Bloomgarden, MD) Aventura Hospital, Aventura, FL (Todd J. Florin, MD) Baptist Health Lexington, KY (Gery F. Tomassoni, MD) Intermountain Medical Center, Salt Lake City, UT (Jeffrey L. Anderson, MD, Allison E. Tonkin, MD) Medical College of Wisconsin, Milwaukee, WI (Jason C. Rubenstein, MD) Methodist DeBakey Heart and Vascular Center, Houston, TX (Dipan J. Shah, MD) Oklahoma Heart Institute, Tulsa, OK (Edward T. Martin, MD) Providence Heart Institute, Southfield, MI (Christian E. Machado, MD) Providence St. Joseph Medical Center, Burbank, CA (Raymond H. M. Schaerf, MD) Scripps Green Hospital, La Jolla, CA (Robert J. Russo, MD, PhD, Jennifer D. Cohen, MD) Scripps Memorial Hospital, La Jolla, CA (Gail T. Tominaga, MD, Steven L. Higgins, MD) The Valley Hospital, Ridgewood, NJ (Aysha Arshad, MD) University of California, Los Angeles, Los Angeles, CA (Noel G. Boyle, MD, PhD) University of California, San Diego, La Jolla, CA (Ulrika Birgersdotter-Green, MD) University of Mississippi Medical Center, Jackson, MS (Andrew L. Rivard, MD) Yale University School of Medicine, New Haven, CT (Rachel Lampert, MD) 1

4 D A T A S A F E T Y A N D M O N I T O R I N G B O A R D Guy Curtis, MD, PhD, Chair, Scripps Green Hospital, La Jolla, CA Michael Smith, MD, Scripps Green Hospital, La Jolla, CA Thomas Ahern, MD, Scripps Green Hospital, La Jolla, CA 2

5 F U N D I N G S O U R C E S T H E M A G N A S A F E R E G I S T R Y W A S F U N D E D B Y G R A N T S O R P H I L A N T H R O P I C G I F T S F R O M : B I O T R O N I K, I NC., L A K E O S W E G O, OR B O S T O N S C I E N T I F I C C O R P O R A T I O N, M A R L B O R O U G H, MA M R. A N D M RS. R I C H A R D H. D E I H L, S A N D I E G O, CA E V E L Y N F. A N D L O U I S S. G R U B B, S C O T T S D A L E, AZ R O S C O E E. H A Z A R D, J R., S A N D I E G O, CA S T. J U D E M E D I C A L, S T. P A U L, MN T H E H E W I T T F O U N D A T I O N F O R M E D I C A L R E S E A R C H, N E W P O R T B E A C H, CA T H E S H U L T Z S T E E L C O M P A N Y, S O U T H G A T E, CA The authors are solely responsible for the concept, design and conduct of the MagnaSafe Registry. The research protocol, the investigational device exemption (IDE) protocol and submission, the formal request to change the Centers for Medicare and Medicaid Services National Coverage Determination (NCD), all data analyses, and the drafting, editing, and submission of the manuscript were all performed without any involvement of the funding sourc es. 3

6 A C K N O W L E D G E M E N T S The authors would like to acknowledge the Nurse Practitioners (including Christina A. Sanders, NP), the Advanced Imaging Fellows (including Jennifer Cohen, MD, and Ashish Kabra, MD), the many Fellows in Cardiovascular Diseases (including Kanae Mukai, MD, Poulina Uddin, MD, Hashim Khan, MD, and Hirsch Mehta, MD), and the MRI technologists at the Coordinating Center (Kristie Tiso, RT-MRI, Leslie Weiss, RT-MRI, and Robert Gaines, RT-MRI) for their long-standing support and tolerance of our research efforts, as well as their unrelenting dedication to excellent patient care. Heather S. Costa, PhD, is acknowledged for her extraordinary talent and effort resulting in the granting of an IDE from the FDA, a modification of the Medicare NCD, and the successful coordination of all aspects of the study. In her role as the Advanced Imaging Fellow, Jennifer D. Cohen, MD (now Jennifer D. Schwartz, MD) was supported in part by the Hewitt Medical Research Foundation, and she contributed significantly to the development of the original research protocol. Lastly, Patricia D. Silva, MS, study biostatistician, is recognized for her enduring commitment to the completion and accuracy of this study and for her career-long uncompromising dedication to high quality investigator-initiated research designed for the improvement of patient care. The MagnaSafe Protocol included on the following pages in this Supplementary Appendix represents a summary of the study protocol as previously published, and it describes how the study was performed and it is without post-hoc changes (Russo RJ. Determining the risks of clinically indicated nonthoracic magnetic resonance imaging at 1.5 T for patients with pacemakers and implantable cardioverter-defibrillators: rationale and design of the MagnaSafe Registry. Am Heart J 2013;165: ). 4

7 MagnaSafe Protocol. Performing MRI with a Pacemaker or ICD (Page 1 of 2) Study participants: A patient with a non-mri-conditional pacemaker or ICD who was a candidate for clinically indicated nonthoracic MRI was eligible for enrollment in the MagnaSafe Registry when magnetic resonance was the imaging modality of choice for a specific disease state or anatomic region without an acceptable alternative imaging modality as determined by the ordering physician. Inclusion criteria: Patients 18 years or older, who were able to provide informed consent, and were scheduled for nonthoracic MRI with a permanent pacemaker or ICD generator from any manufacturer, implanted after 2001, and with cardiac leads of any age from any manufacturer. Exclusion criteria (in addition to standard MRI exclusion): A pacemaker or ICD generator placed prior to 2002; pacing-dependent with an ICD; a generator battery voltage at elective replacement indicator (ERI); presence of an active implantable medical device other than a pacemaker or ICD; presence of epicardial leads or abandoned or non-functional pacing or high-voltage leads with the exception of post-cabg temporary epicardial pacing wires (a chest X-ray could be used to determine the presence of an abandoned lead if questioned, but was not required); presence of an implanted pacemaker or ICD in an abdominal position; and a pacemaker or ICD that was labeled as MRI-Conditional (approved by the FDA for exposure to MRI under specific conditions). Conditions that did not require study exclusion: Prior MRI with an implanted pacemaker or ICD in place was not an exclusion for enrollment. Thus, patients could undergo repeat MRI examinations without limitation. In addition, no limit was placed on the minimum time from generator or lead placement to an initial MRI, or the interval between repeat MRI examinations. Informed consent: Written informed consent was obtained for the purpose of clinical data collection and included a discussion of the risks of clinically performed MRI. Personnel: A qualified physician, nurse practitioner or physician assistant with cardiac device expertise (ICDs and pacemakers) and training in advanced cardiac life support (ACLS) was in attendance for the duration of the MRI examination and was able to observe the patient, the ECG, oxygen saturation, and blood pressure from the time of device reprogramming for MRI until baseline device settings were restored and monitoring was discontinued. A supervising physician with cardiac device expertise and hospital privileges to place a temporary transvenous pacemaker was responsible for oversight of key portions of the study, which included pre-mri device interrogation, assessment of pacing-dependence and post-mri device reprogramming, and was immediately available to provide clinical guidance or urgent medical care if required in the event of a complication. MR imaging: All studies were performed in a 1.5 tesla scanner without vendor restriction. Specific absorption rate limits were not pre-specified (SAR, a measure of the radiofrequency power absorbed per kilogram of body mass), and if reached, imaging settings were changed to maintain Normal Operating Mode. If necessary, the technologist could use First Level Controlled Operating Mode to obtain clinically adequate images; however, this was considered a protocol deviation. Monitoring: Using an MR-compatible monitoring system, pulse oximetry and cardiac rhythm were continuously monitored, and blood pressure was measured every 5 minutes from the time of device reprogramming for MRI until the baseline device settings were restored. While cardiac rhythm may be difficult to identify by ECG during MRI scanning due to radio frequency (RF)-induced artifact, a significant change in heart rate or regularity may be detected by observing the pulse oximetry recording, which is not affected by RF-induced electrical artifact. 5

8 MagnaSafe Protocol. Performing MRI with a Pacemaker or ICD (Page 2 of 2) Pacing dependence: To determine pacing dependence, the minimum pacing rate was decreased in increments of 10 beats per minute (bpm) to 40 bpm, and the underlying rate and rhythm were documented. If the underlying heart rate was <40 bpm, or if the patient described symptoms of lightheadedness or pre-syncope in the upright or supine position with an intrinsic heart rate of 40 bpm, then the patient was determined to be pacing-dependent. If the patient was asymptomatic with an intrinsic heart rate of 40 bpm, the patient was determined not to be pacing-dependent. Pre-MRI device interrogation: For all patients, a new device interrogation was performed pre-mri following a standardized protocol (without inclusion of stored values). Device interrogation included a measurement of battery voltage, P-wave and R-wave amplitudes (when present), pacing lead impedance, and pacing threshold for all leads (when appropriate; at any pulse width). For ICD patients, high-voltage (shock) lead impedance was obtained only if it could be assessed without device discharge. Defibrillation threshold testing was not performed. Reprogramming a pacemaker for MRI: For the patient who was determined to be pacingdependent, the device was programmed to an asynchronous pacing mode (DOO or VOO) at the previously programmed baseline lower rate limit. For the patient with a pacemaker who was not pacing-dependent, the device was programed to a no-pacing mode (ODO or OVO) prior to MRI. If the device could not be programmed to a no-pacing mode, it was placed in a VOO or DOO mode with pacing output and rate set at minimum values. Magnet response was disabled for all patients. Reprogramming an ICD for MRI: For the ICD patient determined not to be pacing-dependent, the device was programed with all bradycardia and all tachycardia functions in an inactive mode (pacing off and tachycardia sensing and treatment functions off) and magnet response was disabled. Pacing-dependent ICD patients were excluded due to the inability to independently program tachycardia and bradycardia therapies for all ICD models available at the time of study design. Post-MRI device interrogation: For all patients, post-mri device interrogation was performed before external monitoring was discontinued and included measurement of battery voltage, P-wave and R-wave amplitudes (when present), pacing lead impedance and pacing threshold (when appropriate) for all leads. For ICD patients, high-voltage lead impedance was obtained only if it could be assessed without device discharge. Defibrillator threshold testing was not performed. Follow up: If Post-MRI minus Pre-MRI setting values did not exceed predetermined limits (battery voltage decrease 0.04 V, pacing lead threshold increase 0.5 V at any pulse width, P-wave amplitude decrease 50%, R-wave amplitude decrease 25%, pacing lead impedance change 50 Ω, or shock lead impedance change 3Ω), then baseline device settings were restored and the patient was scheduled for device interrogation at 3 to 6 months. If any limit was exceeded, then the patient was scheduled for follow-up device interrogation within 1 week, and at 3 and 6 months. If necessary, settings were reprogrammed to maintain an appropriate safety margin for pacing and sensing. Patients were seen in follow up at the discretion of the supervising physician if they had a new-onset arrhythmia, loss of capture (for pacing-dependent patients), electrical reset, or device or lead failure noted during or immediately after the MRI exam. Complications: If the patient experienced new-onset atrial fibrillation or flutter, symptomatic bradycardia, ventricular tachycardia or fibrillation, or loss of pacing capture, the scan was stopped, the patient was moved out of the scanner room, initial device settings were restored, and further treatment was performed as per ACLS protocol or at the discretion of the supervising physician. 6

9 D E S C R I P T I O N O F S T U D Y E ND P O I N T S Primary end points of the MagnaSafe Registry were death during the MRI examination; generator or lead failure requiring immediate replacement that was determined during or at the completion of the MRI examination; loss of capture during the MRI examination for pacingdependent pacemaker patients (pacing-dependent ICD patients were excluded from study enrollment); new-onset atrial or ventricular arrhythmia recognized during or at the completion of the MRI examination that represented a change in rhythm from baseline at the time of scanner entry regardless of a history of arrhythmia; and full or partial generator electrical reset assessed during or at the completion of the examination (as explained below). Exposure of a cardiac implantable electronic device and lead combination to a high-energy RF field during MRI will result in a bidirectional flow of current to both the myocardium and the implanted generator. Current may then flow into the internal circuitry of the generator, reaching the microprocessor and random access memory (RAM), and may result in device malfunction or damage, including memory corruption and changes in programmable device settings. Some programmable settings, such as pacing mode or rate, are stored in a redundant format and then used to generate a final or comparison value. Others, such as patient name or other demographic information, may have a single file location and are thus more vulnerable to corruption. The ultimate source of device setting information (or default settings) is stored in incorruptible or nonvolatile read-only memory (ROM) format. Full Electrical Reset is a software or hardware reset that results in a backup VVI pacing mode (and may include activation of anti-tachycardia therapies for an ICD) and requires full user reprogramming to restore device software operation. The algorithm that leads to this condition is vendor-specific and is usually triggered by a restart of the microprocessor or corruption of a fundamental file, such as pacing mode (or a combination of files). Partial Electrical Reset, on the other hand, refers to corruption of memory affecting one or more files, which does not trigger a software/hardware reset. These files in dynamic memory include information relating to implanting physician, date of implant, and patient identification. 7

10 Secondary end points of the MagnaSafe Registry that were assessed immediately after the MRI examination as Post-MRI minus Pre-MRI values, were battery voltage decrease 0.04 V, pacing lead threshold increase 0.5 V (Danilovic D, Ohm OJ. Pacing threshold trends and variability in modern tined leads assessed using high resolution automatic measurements: conversion of pulse width into voltage thresholds. Pacing Clin Electrophysiol. 1999;22: ), P-wave amplitude decrease 50%, R-wave amplitude decrease 25% and 50% (Chan CC, Lau CP, Leung SK, et al. Comparative evaluation of bipolar atrial electrogram amplitude during everyday activities: atrial active fixation versus two types of single pass VDD/R leads. Pacing Clin Electrophysiol. 1994;17: ), pacing lead impedance change either positive or negative of 50 Ω (Sharif MN, Wyse DG, Rothschild JM, Gillis AM. Changes in pacing lead impedance over time predict lead failure. Am J Cardiol. 1998;82: ), and high-voltage (shock) lead impedance change either positive or negative of 3Ω. These setting change levels or magnitudes are well below a value that would require clinical intervention based on accepted community standards of care. The secondary end points were used to identify patients required to undergo repeat device interrogation within 7 days, at 3 months (±30 days), and at 3 to 6 months (±30 days) after MRI to determine if the observed device setting changes had returned to baseline. Without a secondary end point event, a single, clinically indicated device interrogation was required at 6 months (±30 days). Although limits of change were established for each device setting measured (secondary end point events), all results were intended to be analyzed as continuous variables with the exception of non-numeric values obtained for battery voltage and pacing threshold. 8

11 S T U D Y P A R T I C I P A N T S A total of 1000 pacemaker cases (818 patients) and 500 ICD cases (428 patients) were considered for inclusion in the study and underwent clinically indicated nonthoracic MRI at 19 centers in the United States. In addition, eleven additional cases did not fulfill entry criteria and were excluded from the analysis: five with an MRI-conditional pacemaker, three who underwent a thoracic MRI scan, two who were consented but did not enter the scanner (unstated patient or physician preference), and one who was pacing-dependent with an ICD. 9

12 C A S E O F G E N E R A T O R R E P L A C E M E N T One patient with an ICD placed 5.6 years prior to the examination required immediate generator replacement after MRI. The patient was scheduled for an MRI of the brain with enrollment in the MagnaSafe Registry. The patient was not pacingdependent and thus, by protocol, was eligible for study entry. The protocol called for inactivation of all ICD functions for the duration of the MRI examination (inactivation of both bradycardia and tachycardia sensing and therapy). However, there was an unanticipated delay in the MRI schedule. During that time, device settings were changed several times and ultimately were not returned to the appropriate mode for MRI. Unintentionally, anti-tachycardia functions were left in an active mode, which was a MagnaSafe Registry protocol violation. At the conclusion of the uncomplicated MRI examination, a terminal error was noted upon initial device interrogation that would not allow for user reprogramming to restore device software operation. The device was replaced later the same day. After explantation, the ICD was returned to the manufacturer. Technical representatives of the device manufacturer subsequently found the ICD to be fully functional. The manufacturer determined that anti-tachycardia therapy was inappropriately left in the active mode during the MRI examination. As a result, the device sensed and misinterpreted the rapid radio frequency (RF) MRI pulsesequence as a tachyarrhythmia with a rate consistent with ventricular fibrillation. The device then attempted to deliver defibrillation therapy for an artifact mistakenly interpreted as ventricular fibrillation. Repetitive unsuccessful attempts were made to charge the capacitor within the magnetic field; however, no shocks were delivered. With multiple unsuccessful attempts to treat what was misinterpreted as a tachyarrhythmia, a capacitor charge time-out error was generated with a resulting Fault Code System Error Log Screen or Red Screen. The device had been previously programmed by the manufacturer to default to a non-functional state in this circumstance, not allowing for user reprogramming and requiring generator replacement. 10

13 S U P P L E M E N T A R Y A P P E N D I X F I G U R E S1: M e a s u r e d C h a n g e s i n D e v i c e S e t t i n g V a l u e s ( P o s t - M R I m i n u s P r e - M R I ) (53) (47) Figure S1. Measured Changes in Device Setting Values. 11

14 S U P P L E M E N T A R Y A P P E N D I X F I G U R E S1: P o s t - M R I m i n u s P r e - M R I c h a n g e s i n d e v i c e s e t t i n g s f o r b o t h p a c e m a k e r s a n d I C D s Figure S1. Measured Changes in Device Setting Values. Secondary end points or the measured Post-MRI minus Pre-MRI change in device settings for both pacemakers and ICDs are presented in histogram format. The x-axis represents Post-MRI minus Pre-MRI values. P-wave and R-wave voltage changes are expressed as a percent change and were calculated as (Post- MRI minus Pre-MRI)/(Pre-MRI) x 100. Vertical dashed lines indicate limiting values previously defined as a setting-change event or a secondary end point. An open circle with an arrow symbol at the end of an x-axis indicates the number of values that are beyond the x-axis limit. For each setting, for both pacemakers and ICDs, the data are highly peaked at zero with limited variation from zero. Pacing lead threshold change was measured as a non-standardized, stepped (ordinal) rather than continuous value, thus yielding a non-normal distribution of data due to the method of device interrogation. Legend for Supplementary Appendix Figure S1: Panel A; Change in atrial lead P-wave amplitude, Panel B; Ventricular lead R-wave amplitude change, Panel C; Atrial pacing lead threshold change, Panel D; Ventricular pacing lead threshold change, Panel E; Atrial pacing lead impedance change, Panel F; Ventricular pacing lead impedance change, Panel G; Battery voltage change, Panel H; Shock (High-voltage) lead impedance change (for ICDs only). RV: right ventricle; SVC: superior vena cava; ICD: implantable cardioverter defibrillator. 12

15 S U P P L E M E N T A R Y A P P E N D I X T A B L E S1: P A C E M A K E R M A N U F A C T U R E RS, M O D E L S, A N D C O U N T S Table S1: Pacemaker Manufacturers, Models, and Counts for 1000 Cases Enrolled in MagnaSafe Biotronik (n=23) Boston Scientific (n=176) Medtronic (n=345) St. Jude Medical (n=445) Sorin (n=11) Cylos 3 Accent DR 1 Adapta DR 185 Accent DR 24 Reply DR 2 Cylos DR-T 1 Advantio DR 1 Clarity DDDR 1 Accent DR RF 135 Reply DR Plus 3 Cylos VR 1 Altrua 20 DR 6 EnPulse DR 33 Accent SR RF 24 Reply SR 1 Evia DR 4 Altrua 20 SR 6 EnPulse SR 1 Anthem RF 7 Symphony DR 5 Evia DR-T 4 Altrua 40 DR 11 EnRhythm P1501 DR 23 Frontier II CRT-P 4 Evia SR 1 Altrua 40 DR EL 3 InSync III CRT-P 3 Identity ADx DR 10 Protos DR/CLS 9 Altrua 40 SR 2 Kappa 700 DR 11 Identity ADx SR 1 Altrua 60 DR 42 Kappa 900 DR 17 Identity ADx XL DR 40 Altrua 60 DR EL 30 Kappa 900 SR 1 Identity DR 2 Altrua 60 SR 3 Sensia DR 30 Identity XL DR 16 Contak Renewal TR 4 Sensia SR 5 Integrity AFx DR 3 Discovery SR 1 Sigma 200 DR 4 Integrity SR 1 Entra DR 1 Sigma 300 DR 8 SenTri 1 Ingenio DR 4 Syncra CRT-P 3 Tempo DR 1 Insignia Entra SR 2 Versa DR 19 Verity ADx XL DR 1 Insignia Plus DR 22 Vitatron 1 Victory DR 8 Insignia Plus SR 2 Victory SR 1 Insignia Ultra DR 30 Victory XL DR 24 Insignia Ultra SR 2 Zephyr DR 53 Pulsar Max DR 1 Zephyr SR 7 Pulsar Max II DR 1 Zephyr XL DR 78 Pulsar Max II SR 1 Zephyr XL SR 4 13

16 S U P P L E M E N T A R Y A P P E N D I X T A B L E S2: I C D M A N U F A C T U R E R S, M O D E L S, A N D C O U N T S Table S2: ICD Manufacturers, Models, and Counts for 500 Cases Enrolled in MagnaSafe Biotronik (n=15) Boston Scientific (n=146) Medtronic (n=177) St. Jude Medical (n=162) Lexos VR-T 1 Cognis 100-D 15 Concerto CRT-D 7 Atlas DR 11 Lumax 340 DR-T 3 Confient DR 12 Concerto II CRT-D 5 Atlas II HF 1 Lumax 340 HF-T 1 Contak Renewal 3 HE 9 Consulta CRT-D 21 Atlas II VR 1 Lumax 340 VR-T 2 Energen VR 3 EnTrust AT 11 Atlas Plus HF 3 Lumax 540 DR-T 5 Incepta CRT-D 1 EnTrust VR 1 Atlas Plus VR 7 Lumax 540 HF-T 1 Incepta DR 3 Evera S VR 1 Atlas VR 1 Lumax 540 VR-T 2 Incepta VR 9 Evera XT DR 2 Current Accel DR 2 Livian HE CRT-D 1 Marquis VR 1 Current DR 1 Quadra Assura CRT-D 1 Maximo DR 2 Current Plus DR 14 Teligen 100 DR 28 Maximo II CRT-D 2 Current RF DR 17 Teligen 100 VR 19 Maximo II DR 2 Current RF VR 5 Unify Quadra CRT-D 1 Maximo II VR 3 Ellipse VR 2 Ventac Prism 2 VR 1 Maximo VR 3 Fortify Assura DR 8 Vitality 2 DR 15 Protecta CRT-D 1 Fortify Assura VR 1 Vitality 2 EL DR 2 Protecta DR 4 Fortify DR 38 Vitality 2 VR 6 Protecta VR 4 Fortify VR 5 Vitality DR HE 3 Protecta XT CRT-D 9 Promote CRT-D 1 Vitality DS DR 3 Protecta XT DR 9 Promote Plus CRT-D 5 Vitality DS VR 12 Protecta XT VR 3 Promote RF CRT-D 8 Vitality EL DR 2 Secura DR 17 Quadra Assura CRT-D 8 Secura VR 10 Unify Assura CRT-D 1 Virtuoso DR 23 Unify CRT-D 15 Virtuoso II DR 12 Unify Quadra CRT-D 7 Virtuoso II VR 13 Virtuoso VR 8 Viva S CRT-D 1 Viva XT CRT-D 2 14

17 S U P P L E M E N T A R Y A P P E N D I X T A B L E S 3 : L I S T O F M A G N E T I C R E S O N A N C E I M A G I N G S C A N N E R S B Y M A N U F A C T U R E R A N D M O D E L Table S3. MRI Scanners by Manufacturer and Model Manufacturer MR Scanner Model* # Cases General Electric Echospeed 1.5 Tesla 62 Optima MR450w 1.5 Tesla 51 Signa Excite 1.5 Tesla 41 Signa Excite HD 1.5 Tesla 45 Signa HDx 1.5 Tesla 188 Signa HDxt 1.5 Tesla 118 Signa Infinity 1.5 Tesla 2 Signa Infinity TwinSpeed 1.5 Tesla 1 Signa LX 1.5 Tesla 8 Philips Achieva 1.5 Tesla 24 Intera 1.5 Tesla 8 Siemens Magnetom Avanto 1.5 Tesla 301 Magnetom Espree 1.5 Tesla 43 Magnetom Sonata 1.5 Tesla 14 Magnetom Symphony 1.5 Tesla 594 Total 1500 * All examinations were performed in an MRI scanner with a field strength of 1.5 tesla. Data are presented as cases because some patients underwent more than one MRI examination during enrollment in the MagnaSafe Registry. A case was defined as an instance in which a patient who provided informed consent entered the scanner and underwent MRI of one or more anatomical regions during a single examination session. If the patient returned on a subsequent day for repeat MRI, a separate informed consent was obtained and the data were entered as a unique case. 15

18 S U P P L E M E N T A R Y A P P E N D I X T A B L E S 4 : A R R H Y T H M I A O N S E T O B S E R V E D D U R I N G O R I M M E D I A T E L Y A F T E R M R I Table S4. Arrhythmia Onset Observed During or Immediately After MRI Device Scan site Arrhythmia * Medications Pacing- Dependent History Detection Resolution PM Brain Atrial fibrillation Sotalol, Warfarin Yes Yes On scanner entry 2 days PM Neck Atrial fibrillation Warfarin No Yes Post-MRI 2 days PM Cervical spine Atrial flutter Warfarin Yes Yes Post-MRI Prior to MRI discharge ** PM Brain Atrial fibrillation Warfarin No Yes During MRI Prior to MRI discharge PM Lumbar spine Atrial fibrillation None Yes No Post-MRI 49 hours ICD Abdomen Atrial flutter Amiodarone, Warfarin No Yes Post-MRI Prior to MRI discharge * The onset of a sustained cardiac arrhythmia during the MRI scan for cases documented to be in sinus rhythm at the time of the initial interrogation and entry into the MRI scanner. Medications included any antiarrhythmic medication or oral anticoagulation medication (but did not include an antiplatelet medication). Patients with an underlying heart rate of less than 40 bpm or those who were symptomatic in a sitting or supine position with a heart rate of 40 bpm or greater were determined to be pacing-dependent, and the device was reprogrammed to an asynchronous pacing mode (DOO/VOO) during the MRI examination. If the patient was asymptomatic and had an intrinsic heart rate of at least 40 beats per minute, then the device was programmed to a no-pacing mode (ODO or OVO). A history of atrial fibrillation or atrial flutter documented in the medical record. The patient was not pacing-dependent, however, the pacemaker could not be programmed with pacing functions in an inactive mode or no-pacing mode (ODO or OVO). As a result, the device was programmed to a DOO mode at the minimum pacing rate and output values. ** Required physician-directed implanted device overdrive pacing immediately following MRI for conversion from atrial flutter to sinus rhythm. The device was an ICD (CRT-D) with a left ventricular lead for cardiac resynchronization therapy. PM: pacemaker. ICD: Implantable cardioverter-defibrillator. 16

19 S U P P L E M E N T A R Y A P P E N D I X T A B L E S5: E L E C T R I C A L R E S E T N O T E D A F T E R T H E MRI E X A M I N A T I O N Table S5: Electrical Reset Noted After the MRI Examination Device MRI Exam Pacing Mode Reset SAR Generator Age* Settings Changed PM Lumbar spine Paced (VOO) Partial No 5.7 years All programmed patient information was lost. However, the device serial number and pacing settings remained intact. PM Brain Not paced (VOO pacing mode, with output set at minimum values) Partial No 5.7 years Several settings reverted to default values. However, patient identification, device serial number, and pacing mode remained intact. PM Brain Not paced (VOO pacing mode, with output set at minimum values) Partial No 6.4 years All programmed patient information, device serial number, and baseline pacing mode settings remained intact. However, pacing changed from a bipolar to a unipolar mode. PM Brain Not paced (ODO) Partial No 9.4 years Post-MRI,??? was noted in the Lower Rate setting window; the device remained in an ODO mode without additional changes. PM Lumbar spine Not paced (ODO) Partial No 9.7 years Several pacing settings reverted to default values. Patient identification information was lost. The device remained in an ODO mode. This was a repeat MRI scan. PM Lumbar spine Not paced (ODO) Partial No 9.7 years Patient identification, and device and lead serial numbers were lost. Battery voltage could not be obtained until 7- day follow up. Pacing settings were unaffected. * The interval time in years from generator implant to MRI examination. No patient experienced a full electrical device reset. The device could not be re-programmed to a no-pacing or ODO/OVO mode, and, therefore, the device was paced in a VOO pacing mode, with pacing output and rate set at minimum values. The patient underwent two separate MRI examinations on different days within the MagnaSafe Registry and experienced partial electrical reset after each examination. SAR: The specific absorption rate (SAR) is a measure of the radiofrequency power absorbed per kilogram of body mass during MRI scanning and indicates the potential for tissue heating. PM: Pacemaker. 17

20 S U P P L E M E N T A R Y A P P E N D I X T A B L E S 6 : C O R R E L A T I O N S B E T W E E N P A C I N G L E A D I M P E D A N C E A N D A C H A N G E I N P - W A V E O R R - W A V E V O L T A G E O R P A C I N G L E A D T H R E S H O L D Table S6. Correlations With Pacing Lead Impedance Change* Pacemakers ICDs Variable 1 Variable 2 Correlation Coefficient 95% CI Correlation Coefficient 95% CI Atrial pacing lead impedance Atrial lead pacing threshold to to 0.05 P-wave amplitude to to 0.08 RV pacing lead impedance RV lead pacing threshold to to R-wave amplitude to to 0.21 LV pacing lead impedance LV lead pacing threshold to to 0.07 R-wave amplitude to to 0.15 * Data pertain to leads (for P-wave amplitude, only right atrial leads in a patient with an intrinsic rhythm that could be measured are included; for R-wave amplitude, only right ventricular or left ventricular leads in a patient with an intrinsic rhythm that could be measured are included). The total number of leads among patients enrolled in the study was 1926 for pacemakers and 997 for ICDs. The number of leads used for the determination of secondary end point events may be smaller than the total number of leads within enrolled patients owing to missing data that could not be recovered or verified. The variables P-wave amplitude and R-wave amplitude represent a percent change rather than an absolute change. All other variables are expressed as an absolute change (Post-MRI minus Pre-MRI). A negative correlation is noted. However, only 3% of the variation in right ventricular pacing lead threshold measurement can be explained by a change in right ventricular pacing lead impedance. A positive correlation is noted. However, only 0.6% of the variation in R-wave amplitude can be explained by a change in right ventricular pacing lead impedance. A positive correlation is noted. However, only 1% of the variation in R-wave amplitude can be explained by a change in right ventricular pacing lead impedance. The decision to not perform statistical comparisons between the pacemaker and ICD cohorts was made before enrollment began. RV: Right ventricle. LV: Left ventricle. CI: Confidence interval. ICD: Implantable cardioverter-defibrillator. 18

21 S U P P L E M E N T A R Y A P P E N D I X T A B L E S 7 : C O R R E L A T I O N S B E T W E E N L E A D A G E A N D D E V I C E S E T T I N G C H A N G E S Table S7. Correlations Between Lead Age and Device Setting Changes* Pacemakers ICDs Variable 1 Variable 2 Correlation Coefficient 95% CI Correlation Coefficient 95%CI Atrial lead age Atrial pacing lead threshold to to 0.08 Atrial pacing lead impedance to to 0.06 P-wave amplitude to to RV lead age RV pacing lead threshold to to 0.18 RV pacing lead impedance to to 0.07 R-wave amplitude to to 0.17 LV lead age LV pacing lead threshold to to 0.14 LV pacing lead impedance to to 0.12 * Data pertain to leads (for P-wave amplitude, only right atrial leads in a patient with an intrinsic rhythm that could be measured are included; for R-wave amplitude, only right ventricular or left ventricular leads in a patient with an intrinsic rhythm that could be measured are included). The total number of leads among patients enrolled in the study was 1926 for pacemakers and 997 for ICDs. The number of leads used for the determination of secondary end point events may be smaller than the total number of leads within enrolled patients owing to missing data that could not be recovered or verified. The variables P-wave amplitude and R-wave amplitude represent a percent change rather than an absolute change. All other variables are expressed as an absolute change (Post-MRI minus Pre-MRI). A negative correlation is noted. However, only 1% of the variation in atrial pacing lead threshold measurement can be explained by a change in right atrial pacing lead age. A positive correlation is noted. However, only 1% of the variation in right ventricular pacing lead threshold measurement can be explained by a change in right ventricular lead age. The decision to not perform statistical comparisons between the pacemaker and ICD cohorts was made before enrollment began. RV: Right ventricle. LV: Left ventricle. CI: Confidence interval. ICD: Implantable cardioverter-defibrillator. 19

22 S U P P L E M E N T A R Y A P P E N D I X T A B L E S 8 : R E P E A T MRI E X A M I N A T I O N S W I T H I N T H E M A G N A S A F E R E G I S T R Y Table S8. Repeat MRI Examinations Within MagnaSafe* Number of MRI Exams per Patient Pacemaker Patients (N=818) ICD Patients (N=428) * The number of MRI examinations per patient within the MagnaSafe Registry. A total of 1000 pacemaker cases (818 patients) and 500 ICD cases (428 patients) were enrolled in the study and underwent clinically indicated nonthoracic MRI. A case was defined as an instance in which a patient who provided informed consent entered the scanner and underwent MRI of one or more anatomical regions during a single examination session. If the patient returned on a subsequent day for repeat MRI, a separate informed consent was obtained and the data were entered as a unique case. ICD: Implantable cardioverter-defibrillator. 20

23 S U P P L E M E N T A R Y A P P E N D I X T A B L E S9: S E C O N D A R Y E ND- P O I N T E V E N T S F O R P A C E M A K E R A N D I C D C A S E S W I T H A N D W ITH O U T A P R E V I O U S MRI Table S9. Secondary End Point Events With and Without a Previous MRI* Pacemaker Cases with a Previous MRI? ICD Cases with a Previous MRI? Secondary End Point No (N=772) Yes (N=225) No (N=406) Yes (N=89) Battery voltage decrease 0.04 V no./total no. (%) 2/608 (0.3) 1/192 (0.5) 22/273 (8.1) 2/57 (3.5) Pacing lead threshold increase 0.5 V no./total no. (%) 12/1380 (0.9) 1/427 (0.2) 5/767 (0.7) 3/174 (1.7) P-wave amplitude decrease 50% no./total no. (%) 5/603 (0.8) 2/184 (1.1) 1/276 (0.4) 0/66 (0) R-wave amplitude decrease 50% no./total no. (%) 0/644 (0) 0/198 (0) 1/402 (0.2) 0/89 (0) Pacing lead impedance change 50Ω no./total no. (%) 45/1454 (3.1) 17/442 (3.8) 34/795 (4.3) 7/179 (3.9) High-voltage lead impedance change 3Ω no./total no. (%) N/A 74/498 (14.9) 23/107 (21.5) * The rate of secondary events for cases with and without a prior MRI examination performed with an implanted cardiac device (pacemaker or ICD). A case was defined as a patient who provided informed consent, entered the scanner, and underwent MRI of one or more anatomic regions during a single examination session. If the patient returned on a subsequent day for repeat MRI, then a separate informed consent was obtained and the data were entered as a unique case, and identified as a repeat MRI examination. Information regarding the previous performance of MRI was not available for three pacemaker cases and five ICD cases. The total number of leads among patients enrolled in the study was 1926 for pacemakers and 997 for ICDs. The number of leads used for the determination of secondary end point events may be smaller than the total number among enrolled patients owing to missing data that could not be recovered or verified, or the absence of an underlying rhythm. For battery voltage, total numbers and percentages pertain to cases; for all other settings, total numbers and percentages pertain to leads (for P-wave amplitude, only right atrial leads in a patient with an intrinsic rhythm that could be measured are included; for R-wave amplitude, only right ventricular or left ventricular leads in a patient with an intrinsic rhythm that could be measured are included). The decision to not perform statistical comparisons between the pacemaker and ICD cohorts was made before enrollment began. ICD: Implantable cardioverter-defibrillator. 21